In a major step forward for diabetes research, scientists have developed a lab-grown model of pancreatic islet cells with integrated blood vessels. The breakthrough, led by Professor Maike Sander of the Max Delbrück Center and published in Developmental Cell, could improve both our understanding of diabetes and the development of new cell-based therapies.
This marks the first time that researchers have successfully created vascularized pancreatic islet organoids using human pluripotent stem cells. These clusters, known as SC-islets, include insulin-producing beta cells and mimic the hormone-secreting function of natural pancreatic tissue. Compared to non-vascularized models, the new organoids showed more mature beta cells and higher levels of insulin secretion—closely matching how cells function inside the human body.
“Our results highlight the importance of a vascular network in supporting pancreatic islet cell function,” said Sander. “This model brings us closer to replicating the natural environment of the pancreas, which is essential for studying diabetes and developing new treatments.”
Engineering a Better Model
Organoids, often described as “mini-organs,” are widely used to model diseases outside the body. However, SC-islet organoids have long suffered from a key problem: their beta cells are often too immature to respond properly to glucose, limiting their usefulness in diabetes research.
To solve this, the team added human endothelial cells and fibroblasts to the organoids. Endothelial cells form the lining of blood vessels, while fibroblasts provide structural support. After experimenting with many combinations of cell culture media, they discovered a mix that allowed the cells to survive, mature, and grow vessel-like networks that surrounded and penetrated the organoids.
“Our breakthrough was devising the recipe,” said Sander. “It took five years of experimenting with various conditions, involving a dedicated team of stem cell biologists and bioengineers.”
Vascularization Boosts Maturity and Function
When exposed to high glucose levels, vascularized organoids secreted more insulin than their non-vascularized counterparts. That response indicates the presence of more mature beta cells.
Further investigation showed how vascularization supports maturation. First, the added cells helped form an extracellular matrix—a structure that sends signals to cells and encourages them to mature. Second, endothelial cells released Bone Morphogenetic Protein (BMP), which directly promoted beta cell development.
To enhance the effect, the researchers integrated the organoids into microfluidic devices that simulate blood flow. Pumping nutrient-rich fluids through the vascular network led to even higher proportions of mature beta cells.
“We found a gradient,” explained Sander. “Non-vascularized organoids had the most immature cells. Vascularization improved maturation, and adding flow improved it further.”
Real-World Results in Mice
The team then tested the organoids in diabetic mice. Those transplanted with vascularized SC-islets had significantly better outcomes than those receiving non-vascularized ones. Some mice showed no signs of diabetes 19 weeks after treatment, confirming that the new model functions well inside the body.
These results also support previous studies suggesting that pre-vascularizing SC-islets before transplantation improves their performance.
Toward a More Accurate Model for Type 1 Diabetes
The research opens the door to better models for studying autoimmune diseases like Type 1 diabetes, where the immune system attacks beta cells.
Sander’s team is now building vascularized organoids using cells from patients with Type 1 diabetes. These models are being placed on microfluidic chips and exposed to the patients’ immune cells to better understand how beta cells are destroyed.
“We want to understand how the immune cells destroy beta cells,” Sander said. “Our approach provides a more realistic model of islet cell function and could help develop better treatments in the future.”
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